Centre Hospitalier Universitaire, Oncology Department, Brest, France.
Léon Bérard Cancer Center, Lyon, France.
Lung Cancer. 2019 Oct;136:109-114. doi: 10.1016/j.lungcan.2019.08.010. Epub 2019 Aug 14.
Brigatinib is a next-generation ALK inhibitor initially developed in ALK-positive NSCLC pretreated with crizotinib.
This retrospective multicentric study analyzed ALK-positive advanced NSCLC patients pretreated with at least one tyrosine-kinase inhibitor, including crizotinib, and enrolled in the brigatinib French early access program. The primary endpoint was investigator-assessed progression-free survival (PFS).
104 patients were included (mean age, 56.6 years; never smokers, 61.5%; adenocarcinoma, 98.1%). Patients had received a median of 3 previous treatment lines, including at least 2 ALK inhibitors (mainly crizotinib then ceritinib). At brigatinib initiation, 59.1% had performance status 0-1, 51.9% had ≥ 3 metastatic sites, 74.5% had central nervous system metastases (CNS) and 8.8% had carcinomatous meningitis. Median duration of brigatinib treatment was 6.7 (95% CI, 0.06-20.7) months. Median PFS was 6.6 (4.8-9.9) months for the entire population. For patients who received 2, 3-4 and >4 lines of treatment before brigatinib, PFS was 4.3 (2.5-8.9), 10.4 (5.9-13.9) and 3.8 (0.8-7.4) months, respectively. In the 91 evaluable patients, disease control rate was 78.2%. From brigatinib start, median overall survival was 17.2 (11.0-not reached) months. Among the 68 patients with progressive disease after brigatinib, CNS was involved in 29.4% of cases. Median OS from the diagnosis of NSCLC was 75.3 (38.2-174.6) months.
These real-world results confirm the efficacy of brigatinib in a cohort of patients heavily pretreated for ALK-positive advanced NSCLC.
布加替尼是一种新一代 ALK 抑制剂，最初在克唑替尼预处理的 ALK 阳性 NSCLC 中开发。
这项回顾性多中心研究分析了至少接受过一种酪氨酸激酶抑制剂（包括克唑替尼）预处理的 ALK 阳性晚期 NSCLC 患者，并参加了布加替尼法国早期准入计划。主要终点是研究者评估的无进展生存期（PFS）。
共纳入 104 例患者（平均年龄 56.6 岁；从不吸烟者占 61.5%；腺癌占 98.1%）。患者接受了中位数为 3 线的治疗，包括至少 2 种 ALK 抑制剂（主要是克唑替尼，然后是塞瑞替尼）。在开始使用布加替尼时，59.1%的患者表现状态为 0-1，51.9%的患者有≥3个转移部位，74.5%的患者有中枢神经系统转移（CNS），8.8%的患者有癌性脑膜炎。布加替尼治疗的中位持续时间为 6.7（95%CI，0.06-20.7）个月。整个人群的中位 PFS 为 6.6（4.8-9.9）个月。对于在接受布加替尼治疗之前接受过 2、3-4 和>4 线治疗的患者，PFS 分别为 4.3（2.5-8.9）、10.4（5.9-13.9）和 3.8（0.8-7.4）个月。在 91 例可评估患者中，疾病控制率为 78.2%。从布加替尼开始，中位总生存期为 17.2（11.0-未达到）个月。在 68 例接受布加替尼治疗后疾病进展的患者中，29.4%的患者有中枢神经系统受累。从非小细胞肺癌诊断开始的中位总生存期为 75.3（38.2-174.6）个月。
这些真实世界的结果证实了布加替尼在 ALK 阳性晚期 NSCLC 患者中大量预处理的疗效。
